Enhanced clearance in an artificial kidney incorporating a pulsatile pump

ABSTRACT

A continuous renal replacement therapy (CRRT) device is provided that weighs between 2 and 10 pounds. The CRRT device can be portable, mobile or completely worn on the person of the patient. Blood and dialysate are each pumped in a pulsed or pulsatile manner through a dialyzer such that a significant portion of the peak pulse of the blood flow coincides with a significant portion of a low pulse portion of the dialysate flow. An differential pressure between a dialysate inlet of the dialyzer and the blood inlet of the dialyzer periodically changes from a high differential pressure of between 70 and 120 mmHg for a first time period and a low differential pressure of between −10 and 10 mmHg for a second time period. The frequency of the high and low differential pressure cycle is between about 0.5 and 4 Hz.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of pending U.S. patentapplication Ser. No. 10/940,862, filed Sep. 14, 2004, entitled WEARABLECONTINUOUS RENAL REPLACEMENT THERAPY DEVICE, which is acontinuation-in-part of U.S. patent application Ser. No. 10/085,349,filed Nov. 16, 2001, entitled WEARABLE CONTINUOUS RENAL REPLACEMENTTHERAPY DEVICE all of which are hereby incorporated by reference. Thisapplication further claims priority from pending U.S. ProvisionalApplication No. 60/866,357 filed Nov. 17, 2006, entitled ENHANCEDCLEARANCE IN AN ARTIFICIAL KIDNEY INCORPORATING A PULSATILE PUMP, whichis also incorporated herein by reference.

TECHNICAL FIELD

The present invention is directed to dialysis systems, and moreparticularly to dialysis systems that may be completely and continuouslyworn by a patient or dialysis systems that are portable or mobile.

BACKGROUND

Hemodialysis is a process by which microscopic toxins are removed fromthe blood using a filtering membrane such as a dialyzer. Typically,hemodialysis is administered to a patient in periodic three to four hoursessions. Each session takes place two or three times per week. Thereexists a growing body of research that prefers daily dialysis sinceincreased dialysis time improves outcomes, both in terms of quality oflife and patient longevity. An additional number of researchers believethat continuous dialysis for twenty-four hours a day, seven days a weekwould provide the best outcome for a patient in terms of quality of lifeand longevity. The actual implementation of substantially continuousdialysis has been impossible to date because of technology and costconstraints. Regardless, it is believed that continuous renalreplacement therapy (CRRT) would be an enormous improvement overintermittent dialysis because far more toxins can be removed from theblood using a CRRT device seven days a week and for nearly twenty-fourhours a day.

Some advantages of providing CRRT include an expected decrease inmorbidity and mortality, a decrease in the amount of medicationsrequired, a decrease in fluid intake, a decrease of dietaryrestrictions, and numerous improvements to the quality of life of theend-stage renal disease (ESRD) patients. Present day CRRT machines arestationary, large, heavy machines adapted to provide dialysis,hemofiltration or a combination of both to individual patients. Theexisting CRRT are cumbersome and require electrical connection to120-140 volt AC electrical outlets as well as several feet of tubing toconnect the machine to the patient. In addition, these machines requirea continuous supply of gallons of fresh filtered water to create thedialysate fluid. Furthermore, a patient must remain connected to theexisting heavy and cumbersome CRRT machine for many hours each day,which limits his or her ability to perform normal, everyday activities.

An additional problem with existing dialysis machines is that frequentreconnection and disconnection to the machine requires accessing bloodflow in a patient by puncturing an artiovenous shunt. These shunts onlylast for limited periods of time and subject the patient to infection,clotting and other complications which result in numeroushospitalizations and repeated surgical interventions. Another problemwith existing dialysis machines is as these machines become smaller anda bit more portable, smaller hemofilters or dialyzer filters must beused that does not clog or clot too quickly so that extended orcontinuous dialysis can be performed. A common type of dialyzer includesnine hundred or more cylindrical hollow fibers through which blood flowis provided. The hundreds of cylindrical hollow fibers are contained ina shell or container in which dialysate fluid is circulated around andpast the exterior walls of the hollow fibers. The exterior walls of thehollow fibers or lumens are semi-porous so that impurities in the bloodcan be moved from the blood and into the dialysate. One problem thatoccurs in a dialyzer is the clogging or clotting of blood flow withinindividual hollow fibers. Such clogging of blood flow through the fibersdecreases the effectiveness of the dialyzer's filtration and bloodcleaning properties. Furthermore, it is understood that proteins andother compounds or substances in the blood may clog the pores of thesemi-porous membrane overtime and decrease the effectiveness of thedialyzer filter. If a dialyzer filter is to be in continuous operationtwenty-four hours a day, seven days a week, it is important that such adialyzer be operational for extended periods of time at or near acontinued peak performance without becoming clogged or having itsefficiency decreased significantly during usage. Furthermore, it wouldalso be useful if a dialyzer remained efficient and effective when alow-power pump is used to pump blood there through such that a minimumamount of energy is required for the highest possible clearance ofimpurities from a patient's blood at the lowest amount of requiredenergy.

Dialyzers' membranes have been studied for well over a half of acentury. The initial inventors of dialysis or dialactic therapyunderstand the basics of diffusion and how toxins diffuse across adialyzer's membrane from blood to a dialysate fluid. There are manyfactors that influence diffusion in solute transfer across asemi-permeable membrane. Such factors have been explained in variousprior articles about the workings of a dialyzer. But, again there hasbeen limited or minimal research on providing a dialysis device whereinthe dialyzer operates efficiently over extended periods of time (morethan 15 hours) in order to provide a low power completely wearable orportable dialysis device having a dialyzer with increased efficiencyover that of previous dialysis machines having a dialyzer with amembrane of the same or similar membrane surface area.

SUMMARY

Embodiments of the invention provide a continuous renal replacementtherapy (CRRT) device that weighs between 2 and 10 pounds. The CRRTdevice can be portable, mobile or completely worn on the person of thepatient. Blood and dialysate are each pumped in a pulsed or pulsatilemanner through a dialyzer such that a significant portion of the peakpulse of the blood flow and pressure coincides with a significantportion of a low pulse flow and pressure portion of the dialysate flow.A differential pressure between a dialysate inlet of the dialyzer andthe blood inlet of the dialyzer periodically changes from a highdifferential pressure of between 70 and 120 mmHg for a first time periodand a low differential pressure of between −10 and 10 mmHg for a secondtime period. The frequency of the high and low differential pressurecycle is between about 0.5 and 4 Hz.

In one aspect thereof an exemplary embodiment of the invention providesa continuous renal replacement therapy (CRRT) device. The CRRT deviceincludes a blood pump channel that establishes a pulsed or pulsatileblood flow. The pulsed blood flow is periodic such that each period ofthe blood flow comprises a high blood pressure portion having a firstduration and a low blood pressure portion having a second duration. Thefirst duration and the second duration have a duration ratio betweenabout 3:4 and 4:3. The duration ratio requires that the time durationsof the high blood pressure portion and low blood pressure portions areat least 75 percent (%) of each other. For example, if the high bloodpressure portion of the pulse has a duration of one (1) second, then thelow blood pressure pulse should have a duration of between about 0.75and 1.25 seconds. The exemplary embodiment further comprises a dialysatepump channel that provides a pulsed or pulsatile dialysate flow. Thepulsed dialysate flow is periodic such that each period comprises a highdialysate pressure portion having said second duration and a lowdialysate pressure portion having said first duration. The high bloodpressure portion and said low dialysate pressure portion occur, at leastin part, during a same first periodic time frame. The exemplaryembodiment also comprises a dialyzer or hemofilter. The dialyzercomprises a blood inlet that receives the pulsed blood flow from theblood pump channel. The dialyzer of the exemplary embodiment alsocomprises a plurality of fibers. Each fiber comprises a semi permeablemembrane exterior and a lumen extending the length of the fiber. Thelumen provides a passage through the fiber for the pulsed blood flow toflow. The dialyzer further comprises a blood outlet for the pulsed bloodflow to exit said dialyzer as well as a dialysate inlet for receivingthe pulsed dialysate flow being pumped by the dialysate pump channel.Also the dialyzer has an outer tube that establishes a dialysatecontainer or chamber, about the plurality of fibers. In other words, thefibers are substantially contained in the dialyzer and are within adialysate chamber or container. The pulsed dialysate flow flows throughthe dialysate chamber. The semi permeable membranes of the plurality offibers are the means between each said lumen and said dialysate chamber.The dialyzer includes a dialysate outlet for the pulsed dialysate flowto exit the dialyzer. The combination of the blood pump channel, thedialysate channel and the dialyzer are configured to establish a peakTrans Membrane Pressure (TMP) across the semi permeable membranes of theplurality of fibers and between said pulsed blood flow in the lumens andthe pulsed dialysate flow in the dialysate chamber. The peak TMP occursduring the first periodic time frame. The peak TMP is between about 70mmHg and 120 mmHg.

Various embodiments of an exemplary CRRT device require that the lowblood pressure portion of the blood flow and the high dialysate pressureportion of the dialysate flow both occur, at least in part, during asecond periodic time frame. Furthermore, the blood channel, thedialysate channel and said dialyzer are configured to establish aminimum TMP across the semi permeable membranes of the plurality offibers during said second periodic time frame. The minimum TMP isbetween about 10 mmHg and −10 mmHg.

Additionally in various embodiments on an exemplary CRRT device a dualchannel ventricle pulsatile pump that comprises the blood pump channeland the dialysate pump channel is incorporated into the device. The samemechanical mechanism may be utilized in the dual channel ventriclepulsatile pump to actuate both the blood pump channel and the dialysatechannel.

Furthermore, some embodiments of the invention may be entirely worn onthe person of the user, while other embodiments of the CRRT device arelight weight (e.g., between 2 and 15 pounds while operating) and mobilesuch that they may be moved about a medical facility or within a user'shome.

Some embodiments of an exemplary CRRT device provide blood pump channelthat may provide a pulsed or pulsatile blood flow with a periodic flowrate of between 0.5 and 4 Hz and wherein the dialysate pump channelprovides a pulsed or pulsatile dialysate flow with a same or similarperiodic flow rate. This periodic flow rate of blood has been found tobe the least damaging to the blood cells as they pass through the bloodpump channel and also deter clogging or clotting of the blood in thepump channel, the fiber lumens in the dialyzer, as well as in the semipermeable membranes between the fiber lumens and dialysate within thedialysate chamber portion of the dialyzer. The pulsed or pulsatile bloodflow described herein appears to provide an unexpected washing orpush-pull effect that helps to inhibit clogging for the extendedoperating time periods of exemplary CRRT devices. It should be notedthat exemplary CRRT devices' elements combine in an unexpected mannersuch that the peak TMP that occurs during the first periodic time frameand the minimum TMP that occurs during the second periodic time frameinhibit clogging of the lumens and the semi permeable membranes.

In another exemplary embodiment a continuous renal replacement therapy(CRRT) device is provided that comprises a blood pump channel forproviding a pulsatile blood flow. The pulsatile blood flow is periodicsuch that each period comprises a high blood pressure portion having afirst time duration and a low blood pressure portion having a secondtime duration. The first time duration and the second time duration havea duration ratio of between about 3:4 and about 4:3, this, of course,includes a duration ratio of 1:1. These exemplary embodiments furtherinclude a dialysate pump channel that provides a pulsatile dialysateflow. The pulsatile dialysate flow is a periodic flow such that eachperiod of the flow comprises a high dialysate pressure portion havingthe second time duration and a low dialysate pressure portion having thefirst time duration; wherein said high blood pressure portion and saidlow dialysate pressure portion occur periodically, at least in part,during a same first periodic time frame. The exemplary embodimentfurther includes a dialyzer. The dialyzer comprises a blood inlet forreceiving the pulsatile blood flow. The dialyzer also comprises aplurality of fibers wherein each fiber comprises a lumen extending thelength of the fiber and a semi permeable membrane exterior. The lumen isfor carrying the pulsatile blood flow through a substantial portion ofthe dialyzer. The dialyzer further includes a blood outlet for saidpulsatile blood flow to exit the dialyzer, a dialysate inlet forreceiving the pulsatile dialysate flow, a dialysate compartment areathat is around or about the plurality of fibers, for said pulsatiledialysate flow to flow through; and a dialysate outlet for the pulsatiledialysate flow to exit said dialyzer. The combination of the blood pumpchannel, the dialysate channel and the dialyzer are configured toestablish a peak blood inlet-to-dialysate outlet differential pressurethat occurs during the first periodic time frame. The peak bloodinlet-to-dialysate outlet differential pressure may be in a range ofbetween about 60 mmHg and about 150 mmHg, which provides an unexpectedenhanced amount of toxins from a patient's blood to move across thefiber semi permeable membrane into dialysate contained within andpulsing through the dialyzer.

Additional embodiments of an exemplary CRRT device are configured suchthat the low blood pressure portion and the high dialysate pressureportion both occur, at least in part, during a second periodic timeframe. The blood pump channel, the dialysate channel and the dialyzerare configured to establish a minimum blood inlet-to-dialysate outletdifferential pressure that occurs during the second periodic time frameand that establishes a differential pressure between about 10 mmHg andabout −10 mmHg.

Other embodiments of the invention provide a method of continuous renalreplacement therapy (CRRT). An exemplary method of providing CRRTcomprises pumping blood, by a pulsatile blood pump, to provide apulsatile blood flow. The pulsatile blood flow is a periodic flowwherein each period comprises a high blood pressure portion having afirst time duration and a low blood pressure portion having a secondtime duration. The first time duration and the second time duration havea duration ratio that can range between about 3:4 and 4:3. The method ofproviding CRRT further includes pumping dialysate, by a pulsatiledialysate pump, to provide a pulsatile dialysate flow. The pulsatiledialysate flow, like the pulsatile blood flow, has a period thatcomprises a high dialysate pressure portion having the second timeduration and a low dialysate pressure portion having the first timeduration. The high blood pressure portion and the low dialysate portionoccur, at least in part, during a first periodic time frame. Theexemplary method further establishes a blood inlet-to-dialysate outletdifferential pressure between a blood inlet of a dialyzer and adialysate outlet of the dialyzer; wherein said blood inlet to-dialysateoutlet differential pressure oscillates between a maximum differentialpressure and a minimum differential pressure at a pump frequency ofbetween 0.5 and 4 Hz. The maximum differential pressure has a range ofbetween about 60 mmHg and about 150 mmHg. The minimum differentialpressure has a range of between about 10 mmHg and about −10 mmHg for thepump frequency of between 0.5 and 4 Hz.

All though two separate pulsatile pumps could be used in an exemplarymethod of CRRT, is various embodiments the pulsatile blood pump and saidpulsatile dialysate pump are each a separate pump channel of a dualchannel pulsatile pump and are each operated by a same mechanicalmechanism. Embodiments of the invention utilize a pulsatile blood pumpand a pulsatile dialysate pump that provides an average pulsatile flowrate of between 30 and 90 milliliters/minute (ml/min).

In yet another embodiment of the invention a method of dialysis isprovided that comprises receiving blood in a blood circuit of a dialysisdevice; pumping the blood in a pulsed manner to provide an averagepulsatile blood flow rate of between 30 and 90 ml/min; pumpingdialysate, in a dialysate circuit of the dialysis device, in a pulsedmanner to provide an average pulsatile dialysate flow rate of between 30and 90 ml/min; receiving the pumped blood at a blood inlet of adialyzer; receiving the pumped dialysate at a dialysate inlet of saiddialyzer, to establish a pressure differential between the blood in saidblood inlet and the dialysate in the dialysate inlet that fluctuates ata periodic rate of between 0 mmHg+/−10 mmHg and 120 mmHg+/−20 mmHg;transferring urea molecules from the blood to the dialysate while theblood and the dialysate are passing through the dialyzer; and cleaningsaid dialysate by a filtration means so that the cleaned dialysate canbe reused and recirculated in the dialysate circuit.

Embodiments of the invention provide a method to CRRT that can beperformed by either a completely wearable or a completely portabledialysis device.

Various embodiments of the invention provide one or more pumping devicesthat pump the blood and the dialysate such that a peak flow of saidblood occurs at alternating times with a peak flow of the dialysate.And, various embodiments of the invention are configured such that thepumping of the blood in a pulsed manner comprises providing, in analternating manner, a high blood flow rate portion and a low blood flowrate portion, and wherein said pumping dialysate in a pulsed mannercomprises providing, in an alternating manner, a high dialysate flowrate portion and a low dialysate flow rate portion. The high blood flowrate portion and the low dialysate flow rate portion each occurring, atleast for a majority of their durations, at the same time.

As such, various embodiments of exemplary methods and devices for CRRThave been found to operate to provide enhance clearances in anartificial kidney when a pulsed or pulsatile pump is used in combinationwith other elements discussed herein to produce an unexpected solutionto a problem faced by renal failure patients, but that has never beeneffectively solved to provide a completely wearable or portable CRRTdevice that is operable to enhance the quality of life of such patientsand to unexpectedly resist clogging or clotting of blood in its dialyzerelement.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding, reference is now made to thefollowing description taken in conjunction with the accompanyingDrawings in which:

FIG. 1 illustrates an exemplary portable or completely wearable dialysisdevice diagram in accordance with an embodiment of the invention;

FIG. 2 illustrates a basic configuration of a dual channel pulsatilepump in conjunction with a dialyzer in accordance with variousembodiments of the invention;

FIG. 3 illustrates a test configuration using a roller pump to pumpdialysate and a roller pump to pump blood through fibers in a dialyzer;

FIG. 4 illustrates a single hollow fiber and adjacent dialysate withinan exemplary dialysate chamber of a dialyzer in accordance with anembodiment of the invention;

FIGS. 5A and 5B provide sample experimental result measurements of: a)input and output dialyzer pressures and b) input and output dialyzerflow rates for a combination roller pump and centrifugal pumpconfiguration used in an experimental comparison dialysis device;

FIGS. 6A and 6B provide sample experimental result measurements of: a)dialyzer inlet and outlet pressures and b) dialyzer inlet and outletflow rates for an exemplary dual channel pulsatile pump used inaccordance an embodiment of the invention;

FIG. 7 depicts a graph that reveals experimental result measurements ofthe relationship between ultrafiltration and a modeled Trans MembranePressure (TMP) across a fiber within a dialyzer for both a roller andpulsatile (shuttle) pump configurations;

FIG. 8 depicts a chart providing a comparison of exemplary experimentalresults for a roller pump configuration and an exemplary pulsatile pumpconfiguration;

FIGS. 9A and 9B provide graphs illustrating experimentally calculatedand estimated blood flow, dialysate flow and Trans Membrane Pressuresover the axial length of a dialyzer for a configuration with rollerpumps and a configuration with pulsatile or pulsed pumps;

FIG. 10 provides a graph illustrating experimentally calculated andestimated ratios of convective urea flux across a semi permeablemembrane in a roller pump configuration and in an exemplary shuttle orpulsatile pump configuration;

FIG. 11 provides a chart that provides experimental and numericalresults for urea clearance with a roller pump and an exemplary pulsedpump design for various blood and dialysate fluid flow rates;

FIG. 12 provides a chart that provides experimental and numericalresults for creatinine clearance with a roller pump and an exemplarypulsed pump design for various blood and dialysate fluid flow rates;

FIG. 13 provides a chart that provides experimental and numericalresults for potassium clearance with a roller pump and an exemplarypulsed pump design for various blood and dialysate fluid flow rates; and

FIGS. 14A and 14B provide a graph of the relative concentrationdistribution C/CO along the axial length of an exemplary dialyzer forthe dialysate inlet and the blood outlet in a roller pump configurationand an exemplary shuttle or pulsatile pump configuration.

FIG. 15 is a graph of an exemplary blood and dialysate pressure or flowover time produced by a single dual channel pulsatile pump or twosynchronized pulsatile pumps.

DETAILED DESCRIPTION

Referring now to the drawings, wherein like reference numbers are usedherein to designate like elements throughout, the various views andembodiments of the exemplary enhanced clearance artificial kidneysincorporating a pulsatile pump are illustrated and described, and otherpossible embodiments are described. The figures are not necessarilydrawn to scale, and in some instances the drawings have been exaggeratedand/or simplified in places for illustrative purposes only. One ofordinary skill in the art will appreciate the many possible applicationsand variations based on the following examples of possible embodiments.

An exemplary embodiment of a wearable CRRT device is depicted in FIG. 1.Wearable CRRT device 100 is built into, or is part of a patient wearablestrap, belt or other wearable apparatus 102. The belt or strap 102 mayinclude a pair of end portions 104 that are adapted to be securedtogether by a fastening means (not specifically shown). The endportion/fastening means 104 could be any number of fastening devicessuitable to secure the ends of the waist belt or shoulder strap togetherover the shoulder of the patient. Such fastening means is not limited tosnaps, buttons, buckles, clips, laces, hook and loops, zippers,harnesses, clasps, etc. One embodiment of an exemplary CRRT device 100may be envisioned to be in the shape of an ammunition or military supplybelt. It could also be in the shape of a waist or fanny pack. Otherembodiments may be in the shape of a small backpack. An exemplarywearable CRRT device 100 is to be worn continuously by a patient eitherover or under the patient's clothing. Other embodiments are portabledevices substantially contained in a carry bag, brief case, purse, orbackpack style container.

One or more circuit cards or microcircuits 106 are incorporated withinthe wearable CRRT device 100. A microcontroller 108 is utilized tocontrol and monitor various aspects of the wearable CRRT device 100.Microcontroller 108 is preferably a low or very low powermicrocontroller, but may be substantially any microcontroller adapted tooperate in an exemplary CRRT device 100. One of the many functions ofthe microcontroller 108 is to monitor the battery 110. An exemplary CRRTdevice 100 will operate continuously for at least five hours to aboutthirty hours using, on average, less than 10 continuous watts of power.Some embodiments of the wearable CRRT device 100 will use, on average,less than 3 continuous watts of power. Embodiments of the invention willweigh between two and ten pounds when operating.

The battery 110 is removably installed in the wearable CRRT device 100.The battery 110 may be rechargeable and may be recharged either whilecontained in the wearable CRRT device 100 or while disconnected andremoved from the wearable CRRT device 100. The battery 110 can storeenough energy to power an exemplary wearable CRRT device 100 for atleast five hours and in some embodiments up to thirty or more hours ofcontinuous uninterrupted device operation. The microcontroller 106, byitself, or via additional circuitry, monitors the charge status of thebattery 110. If the microcontroller 106 determines that the battery 110is low on charge or has less than an estimated, predetermined amount ofoperating time left (e.g., one hour left), the microcontroller 106 maytrigger an alarm condition via the alarm circuit 112. Alarm circuit 112may provide any combination of an audio, visual or physical alarm. Thephysical alarm signal may include vibrations or small tingle-styleshocks to the patient. An alarm condition or warning may be displayed ona display 114, which can be seen by the user. The display 114 may be aliquid crystal display, light-emitting diode display or any other lowpower display technology. An alarm condition may also shut down all orpredetermined parts of the exemplary wearable CRRT device 100. Forexample, a battery low condition may slow the pump, discussed hereinbelow, to a very low volume of blood movement through the dialyzer inorder to save energy and decrease a possibility of blood clotting. Thepump may be slowed to one tenth to one half of its normal pumping ratein order to conserve energy until a battery recharge or new battery isprovided.

A moisture sensor 116 is in electrical communication with themicrocontroller 108. The moisture sensor 116 detects high humidity,condensation, or liquid present inside the packaging or covering over(not specifically shown) the wearable CRRT device 100. In someembodiments a plurality of moisture sensors are positioned at strategiclocations within the CRRT device 100. For example, the moisture sensor116 may be positioned near the pump (to be discussed later) or thefiltration and absorption section. In other embodiments, an additionalmoisture sensor may also be located near the dialyzer input and/oroutputs.

The packaging or covering that partially or completely encloses theexemplary CRRT device 100 may be the combination of plastic, cloth, arubberized material, a poly product, or another suitable material. Thecovering may cover a portion of the wearable CRRT device 100 and allowaccess to various parts of the device, such as the display 114 and/orthe user or doctor controls 118.

High humidity, condensation or the presence of liquid inside anexemplary wearable CRRT device 100 may be indicative of patient bloodleakage, dialysate leakage or other fluid leakage inside the CRRT device100. Upon sensing moisture, the moisture sensor 116 provides a signal tothe microcontroller 108 and an alarm is triggered via the alarm circuit112. Depending on the location of the moisture sensor within thewearable CRRT device 100, different responses to sensed moisture mayoccur. For example, if a moisture sensor senses moisture near the bloodcircuit (to be described below) the CRRT device 100 may turn the pumpcompletely off, providing audible alarm to the patient wearer andutilize the wireless communications circuitry 120 to call an emergencynumber for help. Conversely, if moisture is sensed near the filtrationand pad absorption portion 122 of the wearable CRRT device 100, then insome embodiments the alarm circuit 112 may sound an audible orpatient-sensed alarm, slow the pumping rate of the blood and dialysateand make further checks via a gas or pressure sensor for possible aircontamination or bubbles within the dialysate loop of the CRRT device100. It is noted that the wireless communication circuitry 120 may alsobe able to provide the geographic location of the exemplary wearableCRRT device 100 in via a wireless communication 120 to a third party whomay provide help or a service to the patient.

The pump 124 is an electric pulsatile pump. Embodiments of the presentinvention may have a single channel pulsatile pump or a dual pulsatilepump. FIG. 1 discloses a dual channel pulsatile pump 124. Each channelof the dual channel pulsatile pump includes a rubberized tubular portion126 and 128. Each rubberized tubular portion comprises valves at eitherend for directing a fluid flow through the rubberized tubular portion ina main direction (depicted by an arrow on the tubular portion 126 and128). A motor and transmission (not specifically shown) within thepulsatile pump provides a pushing member that oscillates back and forthbetween the rubberized tubular portions 126 and 128 thereby alternatelypressing against the resilient rubberized tubular portions and creatinga pulsed flow into and out of each of the established created chamberswithin the rubberized tubular portions 126 and 128. There are varioustypes of pulsatile pumps. Some such pumps use pneumatic pressure tocause the flexure of the valved chambers of the pump. In someembodiments a pulsatile electromagnetic pump may be used in order tominimize moving parts of the pump. Exemplary dual channel pulsatilepumps would use the same motor and transmission to ultimately pump in apulsed manner both channels of the pump. This saves energy and minimizesthe size of the pumping system within an exemplary wearable CRRT device100. The microcontroller 108 can be used to control various pumpingvariables. Potential adjustable pumping variables include, but are notlimited to, adjusting the pump stroke, the volume per stroke, the speedor number of strokes per minute of each chamber, the torque of the pumpmotor and transmission combination, the pumping rate (i.e., number ofpump cycles per minute), the pump pressure, the pump pressuredifferential between the input and the output of the pump, and pumppause and cycle times. In some embodiments, the pushing member 130 maybe adjusted to press against each of the flexible tubing portions 126and 128 with longer or shorter strokes such that the volume of fluidpumped through one of the channels is larger than the volume of fluidbeing pumped with each pulse of the other channel of the pump. Thepushing member 130 is part of a mechanical mechanism that can pump bothchannels (blood and dialysate) of an exemplary CRRT device.

An exemplary wearable CRRT device 100 has two fluid circuits: a bloodcircuit as indicated by the arrows 132 and a dialysate circuit asindicated by the arrows 134. The dual channel pulsatile pump 124 is usedin the exemplary embodiment. The pulsatile pump may have rubberizedflexible cartridges 126 and 128 that provide flow in a single directionor in opposing directions. The pulsatile pump 124 shown provides flowacross the pump or through the pump in opposing directions. Eachcartridge or pump chamber 126 has an input valve at an input side 134 ofthe chamber and an output valve at the output side 136 of the chamber.The input and output valves are ball values that minimize damage to theblood cells in the blood circuit. Flapper valves may also be used invarious embodiments.

In the blood circuit 132 of an exemplary CRRT device 100, blood from apatient enters the blood circuit at the blood input 138 the blood flowsthrough the blood circuit 132 where anticoagulant fluid (e.g., heparinand other reasonable equivalents) may be mixed with the blood via ananticoagulant reservoir 140 and an anticoagulant micropump 142. Theanticoagulant micropump may be a piezo or diaphragm MRRO pump or othertype of low energy pump for providing small amounts of anticoagulantfluid to the blood flow.

The blood flows past a first pressure sensor 144 prior to entering theinput valve 134 a of the dual channel pulsatile pump. When the pushingmember 130 presses against the flexible rubberized tubular cartridgeportion 126, the input valve 134 a closes and the exit valve 136 a opensand allows a pulse of blood to exit the first pulsatile chamber [126].Additional fluid reservoirs 146 and micropumps 148 may add additionalsubstances to the blood flow, such as anticoagulant fluids ormedications. The blood then passes past a second pressure sensor 150which senses the pressure of the output stroke of the first channel ofthe pulsatile pump prior to the blood entering the dialyzer 152. Anexemplary blood channel pulsatile pump chamber can provide a blood flowrate of between about 15 to 100 ml per minute (pulsatile). An exemplarypulsatile pump 124 may have dimensions of 9.7×7.1×4.6 centimeters with aweight of less than 400 grams when not operating. An exemplary pump usesless than 10 watts of energy to pump two channels of fluids using asingle motor, transmission and pushing member that alternately pumpseach channel in a pulsatile fashion at or around 180 degrees out ofphase. If the pushing means of an exemplary pulsatile pump hasdifficulty compressing or requires very little energy compressing one ofthe flexible rubberized tubular chamber portions, the pulsatile pump mayprovide an alarm to the microcontroller 106 indicating a possibleocclusion in the blood or dialysate circuits input or output valves of apulsatile pump channel. A low power pulsatile pump using from two toabout 7 watts, steady state, may also be used successfully in exemplaryembodiments of the invention.

The pulsatile pump can be tuned by adjusting the motor transmission orre-orienting the pushing member a small distance from being centeredbetween the tubular portions 126, 128 such that the pulses or cycles ofthe two pulse chambers are in phase, 180 degrees out of phase, oralternating such that each chamber pumps at a predetermined number ofdegrees out of phase in order to utilize the pulses of the pump to aidin maximizing the dialysis process occurring in the dialyzer 152.Embodiments of exemplary pulsatile pumps may be slowed such that theblood flow or fluid flow through a chamber of the pump is between 1 and50 ml per minute during an alarm state in the wearable CRRT device 100.

Other types of pumps can also be successfully used or incorporated intoembodiments of the CRRT device 100. For example, two separate pulsatilepumps may be used provided that the pumps can be timed such that thepumps continuously pulse at predetermined alternating output rates. Thiscan be performed with stepper motors and microprocessor control Otherpumps that can provide a pulsed output such as a double-sided pistonpump that has an intake stroke through one valve and a pump strokethrough a second valve may also be used. Such a pump may be magnetic orpneumatically powered.

Still discussing the blood circuit 132, the blood passes by the secondpressure sensor 150 and then through the hollow lumens or fibers of thedialyzer 152 (not specifically shown). The dialysis process takes placein the dialyzer wherein impurities in a patient's blood move via a masstransfer through the outer membranes of the porous lumens through whichthe blood is traveling. The impurities are deposited into the dialysateas they exit the outer surface of a lumen's outer membrane into thedialysate that is flowing through the dialyzer in the dialysate circuit134.

The blood cleaned exits the dialyzer and travels toward the bloodcircuit output 154 to go back into the patient. As the blood flows fromthe dialyzer 152 to the blood circuit output 154, additional medicines,vitamins and other fluids may be added to the blood via reservoirs 156and micropumps 158.

The pressure of the blood as it exits the dialyzer 152 is sensed at athird pressure sensor or transducer 160.

The microcontroller 108 may display pump status or other pump/flowrelated information such as pressure, flow rate, or dual channel pumpphase difference on the display 114. User controls 118, being buttons,switches, slide controls, knobs, connectors, or touch-sensitive switches(not specifically shown) may be used to enable the patient, a physician,a nurse, technician or computer-based device to adjust various settingsand controls on the exemplary CRRT device 100. Furthermore, thecommunication device 120 may be utilized to send and receive controlsettings via a paging or other telecom or wireless communicationchannels or networks for fine tuning or medical adjustment of theexemplary CRRT device. For example, adjustments to the pump 124 rate,flow rate, pump RPM, pulse rate or any of the micropump flow rates mayall be monitored or controlled vial the user interface 118 and 114 orthe wireless communication circuitry 120. A doctor may be able tomonitor the CRRT device from a satellite location and be able to adjustCRRT settings remotely.

The dialyzer 152, is shown as a single dialyzer, but can be a single ormultiple dialyzers connected in series or parallel. The dialyzer 152 maytake the form of a cartridge that can be “clicked” or quick connectedand disconnected into and out of the blood/dialysate circuits by adoctor, nurse or technician. The dialyzer 152 used in an exemplary CRRTdevice 100 may comprise from 0.2 to about 1 square meters of dialyzingsurface area (e.g., semi permeable membrane) on the lumen fiberstherein. During dialysis, the blood circuit 132 generally has bloodflowing in a direction opposite that of the dialysate circuit flowthrough the dialyzer 152. Furthermore, it has been determined throughexperimentation that the pulsing of the pulsatile pumps out of phase aidin maximizing the dialysis process. In particular, embodiments of theinvention that incorporate a out of phase pulsatile blood flow anddialysate flow through a dialyzer provide enhanced clearance withrespect to the removal of toxins from the blood over similar systemsthat do not incorporate a pulsed or pulsatile dialysate in blood flowthrough dialyzer. Such results have been found with exemplaryembodiments even when the dialysate and the blood flow through thedialyzer in the same direction.

The combination of the first, second and third pressuresensor/transducers 144, 150 and 160, provide differential measurementsthat can be analyzed by the microcontroller 108. For example, if thepressure differential across the dialyzer 152 is too high (from bloodinput to output), it may mean, among other things, that the dialyzer 152has multiple clots or occlusions in the fiber lumens therein. A highpressure differential may also mean that the dialyzer is being operatedat too high a blood flow. As a result, an alarm situation can beinitiated by the microcontroller 108 or the blood pump 124 may beautomatically adjusted by the microcontroller to operate at a higher orlower torque, pump rate or pulse volume such that the flow rate isdecreased in predetermined increments in an attempt to stabilize ordecrease the pressure differential so that blood cell damage isminimized. If a pressure at one of the pressure transducers 144, 150,160, drops below a predetermined low pressure, it may be an indicationthat a fluid leak has occurred in the blood circuit or that air is beingpulled into the blood circuit 132. The microcontroller 108 may shut downor slow predetermined parts of the wearable CRRT device 100 in responseto pressure in the blood circuit being measured below a predeterminedlevel. Furthermore, the microcontroller 108 may initiate an alarmcondition in conjunction with the alarm circuit 112 and communicationcircuit 120.

Still referring to FIG. 1, the exemplary dialysate circuit 134 will nowbe discussed. A fourth pressure transducer 162 measures the dialysatepressure at the input side of the dialysate pump cartridge 128. Thefourth pressure transducer or sensor 162 provides a pressure reading atthe input of the dialysate pump cartridge to the microcontroller 108.The dialysate pump portion 128, like the blood pump portion 126 ispreferably part of a dual pulsatile pump device 124 as described above.It is understood that the dialysate pulsatile pump portion may also be aseparate pulsing pump device in varying embodiments.

Cleaned, fresh dialysate from the sorbent filters 122 flows through thedialysate circuit 134 past the fourth pressure transducer 162 and ispumped through the dialysate pump rubberized tubular portion 128. Thedialysate portion of the dual pulsatile pump can pump dialysate at aflow rate ranging from near 0 to about 200 ml per minute (pulsatile).During normal pumping operations the operational flow rate of thedialysate through the dialysate pump is between about 40 to about 100 mlper minute (pulsatile).

Embodiments of the wearable CRRT device 100 are designed to operateusing less than about 1 liter of dialysate. Other embodiments mayfunction properly and only require between 300 ml and 400 ml ofdialysate in the closed dialysate fluid circuit 134. In embodimentsdesigned for young adults or children, the amount of dialysate neededfor operation may be between about 100 to 300 ml of dialysate.Minimizing the amount of dialysate decreases the overall weight of anexemplary device and decreases the operating cost by minimizing theamount of medical waste produced by a dialyzer. The combination ofdialysate and filters 122 allow the embodiment to circulate dialysatefluid for at least twenty-four hours before a filter requiresreplacement. In various embodiments filter replacement may be requiredat intervals between twenty-four and forty-eight hours. Furthermore,because less than a liter of dialysate is all that is needed in theclosed dialysate circuit 134, sterile or ultra-pure dialysate can beeconomically used in exemplary embodiments of the wearable CRRT device100. It is further understood that in embodiments that provide aportable and/or partially wearable CRRT device, the amount of dialysatein the dialysate circuit 134 may be greater than one liter. In fact, theamount of dialysate or ultra-pure dialysate in a portable or mobile orpartially wearable device may range from 300 ml to about 5 or 6 litersof dialysate.

In existing large substantially stationary dialysis machines, it iscommon to use about 90 liters of dialysate per patient per run.Generally, due to the amount of water required to create the dialysate,filtered water, rather than ultra-pure water, is used in such largedialysis machines. Filtered water is much less expensive than ultra-pureor sterile water. Filtered water that is used in large present dialysismachines is allowed to have some bacteria in it. Bacteria are largerthan the size of the pores in the membranes or fiber lumens used withinan exemplary dialyzer 152. Since the bacteria are larger than the poresize in the semi-permeable membranes of the lumens within the dialyzer152, the bacteria cannot cross the membrane and get into a patient'sblood in the blood circuit 132.

Conversely, medical research has provided some results that areuncomfortable with the use of non-sterile dialysate (i.e., dialysatecontaining filtered water, bacteria, toxins, or microorganisms). Medicalresearch has shown that microorganisms and bacteria within non-steriledialysate create waste products, toxins or poisons in the dialysate. Thewaste products from the bacteria can cross the dialyzer porous membraneand get into the patient's blood while the actual bacteria itselfcannot. Such toxins are referred to in some cases, as endotoxins. It hasbeen shown that endotoxins that pass from dialysate through the dialyzermembrane to a patient's blood can have a negative impact on a patient'shealth. The endotoxins may result in making a patient sick.

Since exemplary embodiments of the wearable CRRT device 100 require lessthan one liter of dialysate, it is economically feasible to useultra-pure or sterile water as the main ingredient in making thedialysate.

The dialysate exits the pulsatile dialysate pump portion 128 via theexit valve 136 b in a pulsed pulsatile fashion and passes a fifthpressure transducer 164, which measures the dialysate pressure on thedialysate input side 222 of dialyzer 152. The dialysate in the dialysatecircuit 154 pulses through the dialyzer 152 such that the dialysatemoves in a direction opposite to the flow of the blood in the lumenmembrane fibers in the dialyzer. Furthermore, fluids being relativelynon-compressible, the peaks of the dialysate flow pulses alternate intime with the peaks of the blood flow peaks pulses through the bloodcircuit 132 in the dialyzer. In other words, the pulsed flow of thedialysate through the dialyzer alternates with the pulsed flow peaks ofthe blood through the dialyzer. In some embodiments of the invention,the alternating peak flows of the dialysate fluid and the blood throughthe dialyzer are about 180 degrees out of phase.

While the dialysate is in the dialyzer 152, waste products and toxins inthe blood pass through the membranes of the lumens within the dialyzerand into the dialysate due to diffusion and further in embodiments ofthe present invention due additionally to convection and osmosis forces.The enhanced clearance of toxins from blood that occurs in embodimentsof the invention is achieved in part by the trans membrane pressure(TMP) caused by the alternating pulsatile pumping action and pressuredifferential between the blood within the lumen membranes and thedialysate outside of the lumen fiber membranes.

The dialysate fluid exits the dialyzer 152 and flows through a sixthpressure sensor or transducer 166. The pressure transducer 166 sends asignal to the microcontroller 108 indicating the pressure of thedialysate exiting the dialyzer 152. The sensed pressure may help toindicate a clogged dialyzer, a dialysate leak or other emergencycondition.

The dialysate circuit 134 moves the now used dialysate from the outputof the dialyzer 152 past the pressure transducer 166 and toward thedialysate filter section 122. The used dialysate in this portion of thedialysate circuit 134 contains toxins, contaminants and otherundesirable substances that have been removed from the blood of apatient. The filtration section 122 filters or reacts with thepredetermined substances in the used dialysate in order to recycle thedialysate for continued re-circulation and use in the dialysate circuit.Some compounds or substances that are considered toxins or contaminantsin the used dialysate are urea, creatinine, and ammonia, along withother various substances that are ordinarily removed by a patient'skidney.

In an exemplary embodiment a first filter 168 in the filtration section122 contains urease. The urease is used to filter the used dialysate andfurther functions to break down urea that was removed from the blood inthe dialyzer 152. When urease breaks down, urea, at least two unwantedbyproducts are created. Generally, the two byproducts of broken-downurea are ammonium (ammonia) and carbon dioxide.

The dialysate with the ammonia and carbon dioxide exit the first filter168. The urea is substantially removed from the dialysate, but theammonia and carbon dioxide need to be removed from the dialysate also.The dialysate, ammonia, and carbon dioxide enter the second filter 170.The second filter 170 contains a compound zirconium or zirconiumphosphate (i.e., ZrPx). The zirconium in the second filter 170 capturesthe ammonia. It is understood by those having ordinary skill in the artof dialysis chemistry that various chemicals and derivations thereof canbe utilized to achieve the same or similar results.

The zirconium or second filter 170 will eventually become saturated withammonia. When saturated or near saturation, the zirconium filter 170will become less efficient at removing ammonia from the dialysate. It isnot advantageous to allow ammonia or ammonium to circulate through thedialysate circuit and back to the dialyzer. Thus, in an exemplarywearable or portable CRRT device 100, a sensor 176 is placed in thedialysate circuit after the zirconium filter 170 in order to sense thepresence of ammonia in the dialysate. The sensor 176 may be a pH sensor,an ammonia specific sensor, or a conductivity sensor. Various probe andelectromagnetic style sensors may be used herein to sense conductivitypH or the amount of ammonia in the dialysate after flowing through thezirconium filter. If an ammonia sensor is used, it will sense whether apredetermined amount of ammonia is present in the dialysate. If a pHsensor is used, it would sense whether the pH of the dialysate hasbecome a predetermined amount more alkaline than an acceptable amount,i.e., the alkalinity of the dialysate is outside of an acceptable rangeof alkalinity. As more ammonia is present in the dialysate, thedialysate becomes more alkaline. It is noted that depending on theactual chemicals and absorbents used in the filters, the dialysate maybecome more acidic and as such a sensor would be used to sense the same.If a conductivity sensor is used, it would sense the conductivitychanges of the dialysate. If the conductivity of the dialysate isoutside of a predetermined range then it could be determined thatammonia is increasing in the dialysate. An electromagnetic sensor mayalso be used to sense the conductivity across the dialysate in a mannerthat would sense a changing conductivity (i.e., ammonia) within thedialysate.

The sensor 176 is in electrical communication with the microcontroller108. If the signal provided by the sensor 176 to the microcontroller 108indicates that ammonia within the dialysate exceeds a predeterminedamount (i.e., the pH or conductivity are outside a predetermined range),then the microcontroller may conclude that the zirconium filter 170 isnot absorbing a majority of or a predetermined percentage of the ammoniain the dialysate flow there through. As a result, an alarm condition maybe triggered by the microcontroller 108. The alarm condition mayinstruct the user that one or more of the filter cartridges for filtersections in the filtration section 122 require replacement. The alarmcondition may also decrease the pumping rate or flow rate of one or bothchannels of the pulsatile pump 124. Slowing the pump rate of the dualchannel pulsatile pump 124 may increase the amount of ammonia absorbedby the zirconium filter 170 due to a decreased flow rate of thedialysate there through. Furthermore, the alarm condition may decreasethe dialysate flow rate and increase or decrease the blood flow ratethrough an exemplary wearable or portable CRRT device 100 by adjustingthe position or motion of the pressing means 130.

The sensor 176 that is used to sense the presence of ammonia in thedialysate should be placed after the second filter 170 containing thezirconium phosphate. In other embodiments, the sensor 176 may be placedafter the third filter 174, which contains hydrous zirconium oxide orafter the fourth filter 178, which contains carbon. In other embodimentsof the invention, a single filter may be used containing layers or amixture of the contents of the four filters discussed above.Furthermore, a parallel filter 172 may be placed in parallel withanother filter, for example filter 168, in order to decrease thepressure drop across one or more filters in the filtration section 122.Both filters that are in parallel (i.e., 172 and 176) may each belayered filters with various filtration and adsorbent substancestherein. Furthermore, the layers may be mixed, for example, carbonparticles may be mixed throughout the entire filter among the layers ofurease and zirconium or zirconium phosphate. Furthermore, the zirconiumand zirconium phosphate may be mixed together within one or morefilters. All in all, the filtration section 122 of an exemplaryembodiment may comprise one or more filter cartridges or filters thatreact with or adsorb substances found in the used dialysate such thatthe dialysate will be renewed for continued circulation and usage in thedialysate circuit 134.

The third exemplary filter 174 comprises hydrous zirconium oxide, whichmay further remove contaminants and ammonia from the dialysate. Abubbler, degasser, valve device, or hydrophilic membrane (“degasser”)180 may be part of each of the filters or filtered portions or be aseparate element there from. A degasser 180 is used in an exemplaryembodiment to remove air, carbon dioxide and other gas bubbles that mayform or be found in the dialysate circuit 134. It is important that avery limited amount of gas bubbles go through the dialyzer 152. As such,a degasser 180 should be positioned prior to the dialysate pump portionof the pulsatile pump 124 and after one or more of the filtrationfilters in the filtration section 122 with respect to the dialysate flowdirection in the dialysate circuit 134.

A fourth exemplary filter 178 contains carbon and is used to furtherclean the dialysate of impurities via adsorption. The first, second,third and fourth filter sections 168, 170, 174, 178, may be designed ascombinational or separate filter sections. Each cartridge can beinserted and removed from an exemplary wearable portable CRRT device 100by the patient, doctor, technician, or nurse. Each filter cartridge maycontain layers or combinations of chemicals or adsorbents. In fact, anexemplary embodiment may have a single cartridge filter containinglayers of required substances to clean and refresh the dialysate afterpassing through the dialyzer 152. The cartridges may be installed in aseries, a parallel or a combination of a series and parallel formation.Furthermore, the filter cartridge or cartridges may incorporate adegasser 180 thereon or such a degasser may be separate elementdownstream from one or more of the dialysate filters or the dialysatefilter section 122.

The filter section or individual filter cartridges require replacementat intervals ranging from about twelve hours to forty-eight hours.Through experimentation, if the total volume of all of the combinationsof all the sorbent materials needed, in necessary quantities, combined,will be between 400 cm³ and 2,500 cm³ and will not require changing orreplacement for 24 to 48 hours while the embodiment is pumping dialysateat a flow rate of about 20 to 70 ml/min.

An additive reservoir 182 and micropump 184 may be connected to thedialysate circuit 134 after the filtration section 122, but before thedialysate input side 133 b. Although not specifically shown in FIG. 1,multiple reservoirs 182 and micropumps 184 can be connected to thedialysate circuit 134. The micropump 184 may be any of the micropumpsdiscussed above with respect to the micropump 142. Here, the micropump184 and reservoir 182 may add chemicals and additives that refresh thedialysate and prolong its ability to act as a dialysate. An exemplarywearable CRRT device 100 may have as little as 300 ml to as much asabout 1 liter of dialysate within the dialysate circuit 134. Anexemplary portable CRRT device may have from 300 ml to about 5 liters ofdialysate. It is important for the sorbent section or filtration portion122 to be able to clean and refresh the dialysate continuously as thedialysate circulates about the dialysate circuit 134.

In various exemplary wearable or portable CRRT devices 100,ultrafiltrate or other fluids may be removed from the patient's blood inaddition the dialysis process. If a patient's kidneys are notfunctioning properly, it may be important to remove excess fluids fromthe patient's blood as well as blood contaminants such as urea andcreatinine. In the dialysate circuit between where the dialysate exitsthe dialyzer 152 and enters the filtration section 122 of variousexemplary embodiments, ultrafiltrate/dialysate, along with othercontaminants and fluids obtained via the dialyzer 152, can be tapped offor removed from the dialysate circuit 134. The ultrafiltrate 188 may bedeposited in a bladder or reservoir 190. The bladder or reservoir 190may be contained within or hang below an exemplary wearable or portableCRRT device 100 and be able to store from about 0.1 to perhaps 2 litersof ultrafiltrate fluid. A fullness sensor associated with the fluidbladder 190 is in electrical communication with the microcontroller 108to enable an alarm condition or fluid fullness reading in theultrafiltrate bladder 190 when the bladder fullness reaches a certainlevel or volume. The fluid bladder 190 may also be incorporated into thewearable or portable CRRT device 100 as an empty cartridge that isfilled via a micropump and valve combination (not specifically shown). Afullness sensor 200 may aid the microcontroller to determine thefullness of the cartridge bladder 190 and may turn off the ultrafiltratesupplying pump and provide a signal to the user that the cartridge needsemptying. In various embodiments, the fluid bladder or cartridge 190 maycontain an absorbent material (also not specifically shown) forabsorbing fluid present in the bladder and to prevent sloshing. Theabsorbent material may be cotton, polymer, sponge, a compressedmaterial, powder, a gel, or other material that absorbs fluid and/orlimits the sloshing in the bladder or cartridge. The bladder may bedesigned to expand as it fills. The bladder may press against the microswitch (not specifically shown) when it is full or expanded therebyproviding a fullness signal to the microprocessor 108.

In some embodiments, the ultrafiltrate cartridge or bladder 190 mayincorporate a means for emptying the fluid bladder 202 thereon in theform of a cap, stopper, valve, removable inner bladder tubing orotherwise.

Exemplary embodiments of a wearable or portable CRRT device 100 canprovide therapy to a patient that incorporates basic dialysis, a complexdialysis regime, ultrafiltration and various medicinal therapies to andfor patient. As discussed, there continues to be a growing body ofliterature indicating that increasing dialysis time, which incorporatesboth longer and more frequent dialysis treatments, may be associatedwith improved outcomes and treatment of End Stage Renal Disease (ESRD)patients, both in terms of life expectancy as well as expected morbidityand mortality.

During experimentation with embodiments of the present invention, therewere concerns related to continuous and consistent solute transportacross the membranes of the hollow fibers within the dialyzer 152 forthe extended 24 hour periods of time. Furthermore, additional concernsrelated to potential clotting or clogging of the individual fibermembranes in the dialyzer 152 that would limit the lifespan andusefulness of the dialyzer 152 for less than twenty-four to forty-eighthours. Different types of pumps including roller pumps, centrifuge pumpsand pulsatile pumps were used as a pumping mechanism for the bloodcircuits and dialysate circuits of various embodiments. The differenttypes of pumps all operated and produced a working portable or wearableCRRT device, but the embodiments that incorporated a dual channelpulsatile pump wherein the dialysate circuit 134 and the blood circuit132 were being alternatively pumped in a pulsatile fashion at or about180 degrees out of phase provided some unexpected, positive results. Itwas found that the clearance levels of blood toxins across the hollowfiber membrane dialyzer is higher when an alternating, out of phase dualchannel pulsatile pump was used with respect to in phase pulsatile pumpsor pumps, such as roller pumps and centrifuge pumps were used and which,did not provide as large a pressure differential across the dialyzer'smembranes between the dialysate circuit and the blood circuit.Furthermore, unexpectedly the use of the pulsatile pump decreasedclogging of the hollow fiber dialyzer membranes due to protein buildupor up, clotting or other fluid-flow inhibitors in experimental devicesover experimental configurations that did not incorporate the pulsedpumping provided by a pulsatile pump in both the blood and dialysatecircuits.

The mechanisms of solute transport across the membrane of a hollow fiberdialyzer have been studied for more than half a century. Historically,it appears that pioneers of dialytic therapy were well aware of thediffusion phenomena when they designed dialyzers based oncounter-current mass exchangers. It was soon realized that convectionalso played a role as a mechanism in ultrafiltration and “the solventdrag” phenomena. The factors influencing solute transport acrosssemi-permeable membranes have been summarized in various papersincluding Ronco et al., “Evolution of Synthetic Membranes for BloodPurification,” Nephrol Dial Transplant (2003) 18 [Suppl 7]: vii 10-vii20. In short, blood flow rates greatly affect the clearance of smallsolutes such as urea, but larger solutes are affected mainly byultrafiltration rates.

In the past a push-pull hemodiafiltration (HDF) device provided a rapidforward and backward filtration through a dialyzer. This HDF mechanismled to alternating the flow of body fluid and dialysate across a highflux hollow fiber membrane. Although this technique worked, it hadvarious drawbacks. One of the main drawbacks of conventional push-pullHDF devices are the necessity of a disposable blood reservoir bag thatwas required to prevent flow variation, as well as the difficulty ofmaintaining a trans-membrane pressure (TMP) across the hollow fibermembranes that would not lead to a collapse of the hollow fibers duringback-filtration. One remedy to these push-pull HDF device problems hasbeen to use volume controllers for ultrafiltrate removal and rigidsynthetic hollow fibers made out of polyacrylonitrile, polysulfone, andpolyamide.

An exemplary wearable or portable artificial kidney or CRRT device 100,as shown in FIG. 1 provides a lightweight, belt-type or small portabledevice that is battery operated and utilizes the unexpected advantagesof a low pulsatile flow rate of 40 to 80 ml per minute of blood anddialysate through a dialyzer filter. Such a device can be used toprovide continuous dialysis treatment to patients with End Stage RenalDisease (ESRD) in a manner that may be continuous or substantiallycontinuous for eighteen to about forty-eight hours.

The basic elements of an exemplary wearable or portable CRRT device, asshown in FIG. 1, could be summed and described as comprising thefollowing four main parts or sections. The first section is a dualchannel or dual pulsatile pump (or pumps) 124 that propels blood throughthe device in one channel and dialysate through the device in anotherchannel. Both the blood and dialysate may be pumped at different flowrates. Furthermore, the blood and dialysate are pumped in an out ofphase or counter phase pulsatile fashion such that the peak pumpingpressure of the dialysate and blood channels occurs at alternatingtimes. A second part is a high flux hollow fiber membrane dialyzer 152comprising from 0.2 to about 1 square meter (m²) of membrane surface. Intests conducted of an exemplary device, an AN-69 dialyzer was usedhaving about 0.6 m² of fiber membrane surface. A third part or sectionof an exemplary embodiment comprises a dialysate regeneration system 122comprising one to four specially designed powder or particle filledcanisters or cartridges containing the same or substantially similarsorbents used in the REDY system used in very large clinic size dialysismachines. The dialysate regeneration system may also include reservoirs182 of electrolyte additives including magnesium, calcium, potassium andsodium bicarbonate to the ultrafiltrate path, and a pH-control circuit176 for monitoring and lengthening the usefulness of dialysate flowingthrough an exemplary device's dialysate circuit. A fourth section orpart of an exemplary embodiment may include auxiliary pumps, generallysmall or micropumps 140 for delivering heparin 142 and perhaps othermedications 156 or substances to the blood circuit. An auxiliary pump orvalve 186 may also be included for aiding the removal of ultrafiltratefrom the dialysate circuit. It is understood that each of theseauxiliary or micropumps all are operated at microprocessor controlled108 or pre-specified flow rates.

It is well known that conventional hemodialysis devices use quasi-steadycounter flows of blood and dialysate in a dialyzer. It was believed thatsuch a steady counter-flow of liquids across the hollow fiber membranein a dialyzer may contribute or be responsible for greater or increasedperformance in various dialyzers. Using embodiments of the presentinvention, a study was performed to compare the impact of a pulsatileflow in the transport of solutes in a high flux dialyzer compared withsteady or quasi-steady counter flows in a substantially identical highflux dialyzer. Comparative experimental studies and numericalinvestigations were deployed to clarify and verify the roll ofparameters influencing the transport phenomena across a dialyzer'smembrane when counter-phased pulsatile flow is used in both blood anddialysate circuits of an exemplary portable or wearable CRRT device ascompared to using the same CRRT device with a standard power hungryroller pump commercially used in dialysis equipment. It should be notedthat the flow generated by a commercial roller pump somewhat resemblespulsation of either blood or dialysate provided by a pulsatile pump butwith a significantly lower amplitude. The following equations have beenadopted to assess the clearance and standard weekly urea Kt/V asmeasures for evaluating the solute removal efficiency of a high fluxdialyzer in the comparative investigations.

$\begin{matrix}{{clearance} = {{Flow}\frac{\left\lbrack {\Delta\mspace{14mu}{Solute}} \right\rbrack}{\left\lbrack {{Solute}\mspace{14mu}{in}} \right\rbrack}}} & {{Equation}\mspace{20mu} 1a} \\{{{Standard}\mspace{14mu}{weekly}\mspace{14mu}\frac{Kt}{V}} = \frac{\left( {{Effective}\mspace{14mu}{Clearance}} \right) \times ({Time})}{\left( {{total}\mspace{14mu}{body}\mspace{14mu}{water}} \right)}} & {{Equation}\mspace{20mu} 1a}\end{matrix}$

Equation 1a can be applied to both the blood side and dialysatecompartments of an exemplary dialyzer. Equation 1b accounts for theeffects of solute distribution volume in blood, in interstitial spaceand recirculation.

The comparison study was performed to provide data that explains theenhanced clearances provided by a dual channel pulsatile pump in anexemplary wearable or portable CRRT device. The experiments andcomparison study provided support for the hypothesis that the enhancedclearances of exemplary pulsatile pumped devices are due tocounter-phased pulsatile blood and dialysate flows generated by thepulsatile pump(s) along with pulse created washing out effectsestablished by the time-dependent flow inside the hollow fibers of thedialyzer. Such washing-out effects prohibit near-wall accumulation oflarge molecules. The large molecules may include proteins and otherlarge substances that may be found in a patient's bloodstream but do notreadily pass through the fiber membranes into the dialysate.

Referring now to FIG. 2, an exemplary configuration of a wearable orportable CRRT device in accordance with embodiments of the presentinvention is shown. This portion of the CRRT device 100 mainly depictsthe dual channel pulsatile pump 124 and the dialyzer 152. This figure isprovided to help explain the comparative results of experiments andstudies being due to the impact of an alternating pulsatile flow ofblood in the blood circuit 132 and dialysate in the dialysate circuit134. The pressure sensors, reservoirs and micropumps and other elementsdepicted in FIG. 1 are not included in the FIG. 2 to eliminate somefigure clutter. Furthermore, FIG. 3 depicts a similar portion of awearable or portable CRRT device as in FIG. 2, except that large, heavy,power-inefficient roller pumps or centrifuge pumps (standard pumps) areused to pump blood through the blood circuit 302 and dialysate throughthe dialysate circuit 304. This dual standard pump configuration 300 is,like FIG. 2, drawn without including pressure sensors, micropumps,reservoirs and various other details depicted in FIG. 1.

Referring to both FIGS. 2 and 3, the dialyzer 152 is the same in bothconfigurations. The particular dialyzer 152 is shown with only onehollow membrane lumen 212 extending the length “L” 210 of the dialyzer152. It is understood that in a real exemplary or actual dialyzer therewould be hundreds of hollow lumens (fibers) extending the length L ofthe dialyzer for the blood to pass through in the blood circuit 132. Themembrane 214 on the outside of the membrane lumen 212 is the membranethrough which mass transport of solutes, including toxins, cross or passthrough the membrane 241 from the blood circuit 132 to the dialysatecircuit 134. Dialysate flows through the dialyzer via the dialysatecompartment 216. The blood flowing in the blood circuit 132 enters thedialyzer via the blood input 218 (B_(i)), travels through a plurality oflumen membranes 212 and exits the dialyzer via the blood output 220(B_(o)). Similarly, in the dialysate circuit dialysate flows into thedialysate compartment 216 via the dialysate input or inlet 222 whereinthe dialysate travels the length 210 of the dialyzer and exits thedialyzer compartment 216 at the dialysate output or outlet 224 andcontinues on through the remaining portion of the dialysate circuit 134.

Referring to FIG. 2 specifically, the dual channel pulsatile pump 124uses a 2-5 watt DC motor to move the pushing element 130 in anoscillating fashion back and forth against the flexible bloodcompartment 126 and dialysate compartment 128. In FIG. 2, the pushingmeans 130 is shown to be pressing against the dialysate flexible chamber128 thereby pushing dialysate in the direction of the arrow 125 withinthe chamber through exit valve 136 b while the input valve 133 b of thedialysate chamber is held in a closed position. The pushing member thenmoves toward the flexible blood chamber 126 decompressing the flexibledialysate chamber 128. Decompression of the dialysis chamber 128 closesthe dialysate output valve 136 b and opens the dialysate input valve 133b. Meanwhile, as the pushing mechanism 130 presses against the flexibleblood chamber 126 within the dual channel pump, the blood within thechamber is forced to exit the output blood valve 136 a while the inputblood valve 133 a remains closed. In this manner, an exemplary dualchannel pulsatile pump provides counter-phased or alternating phased or180 degrees out of phase pulsatile flows of the appropriate fluidsthrough the blood and dialysate circuits. It is understood that apulsatile pump may be manufactured in a variety of ways such that twochambers of fluids can be made to pump at alternating times. Suchcounter flow or alternating pump peak moments may be 180 degrees+/−about90 degrees out of phase. Exemplary embodiments do not require that thedialysate flow and the blood flow be at the same rate in ml per minutedue to the two fluids having different viscosities. Furthermore, thedual channel pulsatile pump may pump the fluids in the same or oppositedirections. Furthermore, the pumps may be comprised of two separatepumps so long as the alternating aspect of the pulsatile pumping ismaintained. In other words, as one chamber of the exemplary pulsatilepump is filling with fluid that the other chamber of the pulsatile pumpis propelling fluid out of its chamber and into its designated fluidcircuit. Such an alternating pump mechanism allows for a peak pressureto be obtained in one circuit near the same time that a minimum fluidpressure is obtained in the other fluid circuit.

The dialyzer 152 may comprise fibers having from 0.2 to about 1 m² inmembrane surface area about the hollow membrane lumens.

Referring now to FIG. 3, a standard roller pump 306 is used to pumpblood through the blood circuit 302 while a similarly standard dialysatepump 308 was used to propel dialysate to the dialysate circuit 304. Theblood pump 306 and dialysate pump 308 are similar in structure anddesign to roller pumps used in prior art dialysis machines. Duringcomparisons of the two configurations (FIG. 2 and FIG. 3) ultrasonicequipment was used to visualize blood and dialysate flows through theirrespective circuits. Furthermore, pressure sensor and measuringequipment were used to measure blood input pressure at the blood inputB_(i) of the dialyzer 218 and blood output pressure at the blood outputB_(o) of the dialyzer 220 as well as dialysate input pressure at theinput of the dialyzer 222 and dialysate output pressure at the output ofthe dialyzer 224. In the comparative experiments, dialysate and bloodwere pumped via the dual pulsatile pump at flow rates of about 40, 50,60 and 80 ml per minute (pulsatile). Furthermore, the pH of thedialysate was sensed via a pH probe located in a position after thefiltration section, but prior to the dialysate being pumped into thedialyzer. Appropriate additives such as sodium bicarbonate were added tothe dialysate to maintain the pH of the dialysate between 7.3 and 7.5.

The dialyzer 152 contained approximately 4,500 lumen membranes eachhaving a length L 210 of about 15 cm. FIG. 4 shows the length L 210 of15 cm and the inner radius of each lumen membrane R1 being about 120micrometers. The outer radius of the exemplary lumens R2 was about 170micrometers. Thus, the thickness of the membrane 214 about the lumen isequal to R2−R1 or about 50 micrometers thick. The diameter of thehemofilter was about 33 mm. FIG. 4 is obviously not drawn to scale butis provided to show a single hollow fiber 212 extending a length 210 ofthe dialyzer having blood flowing within its inner radius R1 anddialysate flowing outside of the outer radius R2 of the fiber 212 in thedialysate chamber or compartment 216. Solute will be transported fromthe blood in the center of the fiber lumen 212 through the membrane 214and into the dialysate compartment 216.

For the standard or roller pump configurations, pumping rates were madesimilar to the pulsatile pump rates provided in the dual pulsatile pumpembodiment such that the blood and dialysate flow rates in theconfiguration of FIG. 3 with the standard pumps 306 and 308 were alsoabout 40, 50, 60 and 80 ml per minute.

Comparisons of the input and output pressures of the dialyzer'sdialysate inputs and outputs as well as the blood inputs and outputswere compared in both experimental configurations. Furthermore, theclearance of toxins and solutes were carefully studied based on samplesof dialysate going in and coming out of the dialyzer as well as samplesof blood going in and out of the dialyzer.

Unexpected clearance results occurred and were measured in thecomparative dialysis configurations using different pumps. Inparticular, the clearance of the pulsatile pump configuration of FIG. 2was significantly higher than the clearance of the standard roller pumpconfigurations. Clearance is referred to as the overall removal orclearance of toxins and solutes from the blood as it passes through thedialyzer. Furthermore, ultrafiltration of the blood occurred withrespect to energy required, more efficiently using the exemplary dualchannel pulsatile pump configuration than using a standard roller orcentrifocal pump configurations. Although measurements could only betaken at the inputs and outputs of the dialyzer, speculation can be madeto try to explain what is occurring within the dialyzer between thedialysate circuit and the blood circuit and across the fiber membranes.The results of the comparison are described in more detail below.

The results of testing configurations using exemplary dual channelpulsatile pump 124 in comparison with two standard roller pumps one forblood 306 and one for the dialysate circuit 308. Flow rates andpressures were sensed at the dialyzer blood input 218 and dialyzer bloodoutput 220. Pressure and flow readings were also sensed at the dialysateinput 222 and dialysate output 224. Flow rates were measured using highresolution Doppler ultrasonography and pressures were sensed usingmicropressure sensors. Results of the testing were divided into twocategories; a first category was the ultrafiltration results and thesecond category was the clearance results. It was determined that theultrafiltration output of the dialyzer was found to be mathematicallyproportional to the pressure difference between the blood within thedialyzer lumens and the pressure of the dialysate in the dialysatecompartment 216. The measurements were taken during a steady-stateoperation of an exemplary embodiment; thus, there was a preload pressurein the inlet to an afterload pressure in the outlet from the pumps. Thepreload was induced by the pump head pressure and the afterload wascreated by the resistance of the dialysate filtration and absorptionsection 122 of an exemplary embodiment.

The ultrafiltration characteristics are depicted with additionalexperimental results in FIGS. 5A, 5B and FIGS. 6A, 6B. In FIGS. 5A and5B, experimental results providing pressures and flow rates at thedialyzer inputs (inlets) and outputs (outlets) are shown along with anultrafiltration output for the roller pump configuration. In FIGS. 6Aand 6B pressures and flow rates for the input and outputs of thedialyzers are shown along with the ultrafiltration output for theexemplary pulsatile pump configuration. In each situation, the pressuresand the flow rates at the inlets and outlets of the dialyzers along withthe ultrafiltration rate is shown. The pulsatile pump configuration inFIG. 6A generates a time-dependent flow of blood and dialysate throughthe dialyzer. In particular, the input and output peak or maximum bloodpressure pulses 402 and 404 are generally about 180 degrees out of phasewith the dialysate input and output peak or maximum pressures 406 and408, respectively. The time duration or length of the high bloodpressure portion 405 of the periodic blood pulse flow may be longer orshorter than the length of the low pressure portion 407 the periodicblood pulse flow. The time duration of the high and low blood pressureportions may have a ratio of from about 4:3 to about 3:4. Ideally, theration would be 1:1, but is not specifically necessary for goodclearance results. The blood pressure at the input 402 and bloodpressure at the output 404 of the dialyzer for the pulsatileconfiguration ranged from about 0 to +60 mmHg. Meanwhile, the dialysatepressure at the input 406 and dialysate pressure at the output 408 areat or near their pressure minimums of between about −90 to −60 mmHg whenthe pressure of the blood is near its peak of between 55 and 60 mmHg.The time duration of the dialysate pressure minimums 409 is similar inlength and overlaps fifty percent (50%) or more of time duration of theblood pressure maximum duration 405. Furthermore, the dialysate inputand output pressure 406, 408 are at their maximums of about 0 mmHg whilethe pressure of the pulsed blood flow at the input 402 and output of thedialyzer 404 are at their minimum pressures of about 0 to 10 mmHg thusshown in FIG. 6B. The time duration of the dialysate input and outputpressure maximums 411 overlap at least about fifty percent (50%) of thepulsed blood pressure during its minimum time duration 407. In FIG. 6 b,one can see that when the difference between the blood pressures at theinput and output 402, 404 is greatest with respect to the pressures ofthe dialysate at the input and output 406, 408, the flow of dialysate410 is at or near its maximum. It is also important to note that thedifference in pressures between the dialysate flow through the dialyzerand the blood flow through the dialyzer appears, at the input andoutputs of the dialyzer to be in a range of about 120 mmHg+/−20 for amaximum difference and 10+/−10 mmHg for a minimum pressure difference.

Looking at FIG. 15, an ideal, yet easier to understand graph of theoutput pressures of the blood channel pulsatile pump and the dialysatechannel pulsatile pump is shown. The periodic dialysate flow 500 has amaximum pressure duration period that overlaps the minimum pressureduration period of the periodic blood flow 502. This over lap 504coincides with the over lap of dialysate maximum duration portion 411and blood minimum duration period 407 of the actual experimental resultsin FIG. 6A. Furthermore back in FIG. 15, the minimum pressure durationportion of the dialysate flow 500 overlaps or coincides in time with themaximum pressure duration portions of the periodic blood flow 502. Thisoverlap 506 coincides with the overlap of the dialysate minimum pressureduration portion 407 and the blood maximum pressure duration period ofthe periodic blood flow 405 of the actual experiments results of FIG.6A. The head pressures caused by the filtration and adsorption portion122 and the blood and dialysate inlet and outlet ports appear to haveestablished the unexpected increased TMP across the fiber membranes thatresults in a enhance clearance of toxins from the blood flowing throughthe dialyzer. The enhanced clearance is achieved using very little powerinto the pulsatile pump or pumps that may be incorporated intoembodiments of the invention.

In FIG. 15, it should also be noted that the lengths or time durationsof the high pressure pulses (and high flow rates) for the dialysatefluid flow 500 should be substantially the same as the lengths or timedurations of the low pressure pulses (or low flow rates) of the bloodflow 502. The ratio of the dialysate high pressure pulse duration to thedialysate low pressure pulse duration should have a ration range that isbetween 3:4 and 4:3. It follows that the lengths of the dialysate lowpressure pulses (and low flow rates) should be substantially the same asthe length or time duration of the high pressure blood pulses (or highflow rates). This is useful in embodiments of the invention forsynchronizing two separate pulsatile pumps. Such dual separate pulsatilepumps could be synchronized using digital stepper motors or by havingdigital sensors sensing rotational positions of a motor and adjustingmotor speeds with a motor controller circuit.

Looking at FIG. 5A, the roller pump configuration, one immediately notesthat the pressure difference between the blood input and output and thedialysate input and output has a small pressure differential range. Thedifference between the average of the input and output blood pressure,at any point in time, with the average of the dialysate input and outputpressure, ranges from about 0+/−5 mmHg and about 35+/−7 mmHg ofdifferential pressure. FIG. 5B shows a significantly lower amount ofultrafiltrate 510 being produced by the roller pump configuration overtime than being produced by the pulsatile pump configuration of theexemplary embodiment shown in FIG. 6 b. Also note that although theroller pump provides some element of pulsation in the blood flow, thedecreased pressure part of the roller pump's pulse is much shorter thanthe decreased pressure part of the blood pressure pulse in the pulsatilepump configuration of FIG. 2. Thus, the peak pulse/min pulse duration ofpulsatile pump configuration are substantially similar in time length(i.e., +/−10%). Furthermore, the maximum amount of pressure provided bythe roller pump configuration, at similar blood flow rates, as in thepulsatile pump configuration is a longer pulse than the pulsatile pumpconfiguration. The blood pressure at the input and output of thedialyzer achieved with the roller pump configuration is generally about20 mmHg or more lower than the peak pressures of the blood pressuressensed at the input and output of the dialyzer in the pulsatile pumpconfiguration. This was an unexpected result as the pulsatile pump usesonly about 3 watts or less of energy to produce the flow rates providedwherein the roller pumps of the roller pump configuration requirestwenty to fifty watts of energy to provide the similar blood flows ratesand pressures as shown in FIG. 5.

Referring back to FIG. 6 b, one can see that the flow rate through thedialyzer with the pulsatile pump configuration varies in a somewhat ornear sinusoidal pattern for both the dialysate and blood flow. Themaximum and minimum flow rates of the dialysate and blood flow (peak topeak) range from about 5 ml per minute to about 20 ml per minute. Assuch, the fluids traveling through the dialyzer are accelerating indecelerating in a regular pulsatile pattern. Conversely, the flow ratesshown in FIG. 5B in the roller pump configuration tend to maintain asteady state for about 4 seconds and then decelerate and acceleratequite rapidly in a negative pulse for a period of about 1 second. Assuch, the acceleration and deceleration within the roller pumpconfiguration is very short-lived when compared to the steady statepulse of the same.

FIG. 7 provides the ultrafiltration rate when compared to the peaktransmembrane pressure (TMP). The TMP is the difference in pressurebetween the blood within the lumen of the dialyzer 212 and the dialysatewithin the dialysate compartment 216 of the dialyzer filter. As shownthe ultrafiltration rate depends greatly on the peak TMP; however, theultrafiltration dependence on TMP appears to be nonlinear. This findingis also unexpected as the present practice and understanding ofultrafiltration in a dialyzer is believed to be linear relationship withrespect to TMP. This unexpected result of a nonlinear ultrafiltrationdependence on TMP was shown by a best fit of a second order polynomialto the experimental data points of the roller pump configuration of FIG.3 and separately for the exemplary dual pulsatile pump configuration ofFIG. 2. The slopes obtained for the pulsatile pump configuration werelarger than the slopes obtained for the roller pump configuration but,only by a small margin. The small margin of improved ultrafiltrationcapability may be very significant as an exemplary wearable or portableultrafiltration device is worn or used on a patient for extended periodsof time. The significance is that additional ultrafiltrate may beremoved from a patient's blood using a pulsatile pump configuration,which requires much less energy than a roller pump or centrifugal pumpconfiguration and provides substantially similar blood and dialysateflow rates through a dialyzer. Furthermore, the push-pull-like movementcreated by the pulsatile pumps and the associated washing effect on theinner walls of the fibers may also play a role in the added efficiencyof exemplary embodiments of the invention.

The experimental results of the clearance levels provided similarlyunexpected results via the experimentation. In the experimental setup ofthe exemplary embodiment using a dual channel pulsatile pump, the dualchannel pulsatile pump was operating at a pulsatile rate of about 2hertz. It is understood that a larger pulse chamber tubular pump chamberor smaller pump chamber would enable a pulsatile pump to operate anoscillation frequency of between about half a hertz to about 4 hertz.Pulsatile pumping at a rate higher than 4 hertz might be damaging to theblood cells in the blood flow, but would probably be acceptable for thedialysate circuit. It is believed that the best pulsed flow rate for theblood and dialysate should be between 1 and 3 hertz such that theliquids flow at rates between about 20 and 100 ml/min.

In the dialysate compartment, the dual channel pulsatile pumpestablishes a relatively large pulsed negative pressure leading to alarge transmembrane pressure (TMP) having a peak of about 140 mmHg, butgenerally ranging between around 70 and 120 mmHg. A TMP caused by thepulsatile or shuttle pump is more of a general approximation due to theimperfect out of phase or counter-phased pulses of fluids (i.e., bloodand dialysate) flowing through the dialyzer and opposing directions.Furthermore, pressure measurements were only made at the inputs andoutputs of the dialyzer because the actual TMP across a membrane insidethe dialyzer could only be computer modeled.

The ultrafiltration rate in the pulsatile pump embodiment isunexpectedly large relative to the blood flow rate (30-50%). It wasdetermined that in a pulsatile pump configuration, the convection ureatransfer is about 31% of the total urea transfer while in the rollerpump configuration, the convection urea transfer was only about 17%. Itis believed that the larger convection contribution to the urea transferin the pulsatile configuration is a significant part of the reason whythe exemplary pulsatile configuration is a superior configuration for awearable or portable CRRT or artificial kidney design. FIG. 10 depictsthe difference in the ratios of convective urea flux to the total ureaflux across a membrane. Here it is easy to see the additional convectiveurea flux provided in the pulsatile pump configuration across the axiallength of the dialyzer.

Referring to FIG. 8, a quick comparison of a roller pump configurationand an exemplary pulsatile pump configuration is shown. The blood flow(Q_(b,in)) into both the dialyzer of the roller pump and pulsatileconfiguration as well as the dialysate flow (Q_(d,in)) are both similarflow rates. The test results show that the ultrafiltration from thepulsatile pump provided more than twice the amount of ultrafiltrate (UF)for similar flow rates of the blood and dialysate into the dialyzer.Furthermore, the differential pressure between the pressures of theblood coming out of the dialyzer with respect to the pressure of thedialysate coming out of the dialyzer produced a much higher peak TMP inthe dialyzer using the exemplary pulsatile pump configuration.

FIGS. 9A and 9B graph a calculated pressure distribution along the axialdistance L 210 of the dialyzer in both the roller pump configuration andan exemplary pulsatile or shuttle pump configuration. The maximumpressure distribution is shown. The pulsatile pump configuration showsthat on the dialysate side, the pressure increases from about −32 mmHgat the dialysate output side of the dialyzer and it increases to about−28 mmHg at the dialysate input side of the pulsatile pump at about 15cm. The pressure of the blood at the blood input side of the dialyzerdecreases slightly from about 23 mmHg to about 20 mmHg at the outputside of the dialyzer. Thus, producing an unexpectedly high peak TMPranging from between 48 to about 55 mmHg across the axial distancebetween the dialysate and the blood flows of the dialyzer. FIG. 9Aindicates that the maximum TMP in a dialyzer using the roller pumpconfiguration is much lower, about 50% or more, than the pulsed maximumTMP established in the exemplary pulsatile pump configuration.

FIGS. 11, 12 and 13 provide comparisons of the urea clearance, creatineclearance and potassium clearance achieved in the roller pumpconfiguration and an exemplary pulsatile pump configuration of awearable or portable CRRT or artificial kidney device. It is noted fromFIGS. 11, 12, and 13 that for a similar dialyzer input flow rate at theblood input 218 and the dialysate input 222, the TMP and resultingclearance of the urea, creatine and potassium is always greater in theexemplary pulsatile pump or pulsed flow configuration of the exemplaryembodiment.

Based on detailed studies and numerical investigations, it is determinedthat the flow of solutes across a dialyzer membrane varies dependingupon the pumping mechanism used to move the dialysate and blood throughthe dialyzer. In particular, it has been determined that the use of adual channel pulsatile pump configuration, wherein one pumping channelis for dialysate and a second pumping channel is for blood and where thechannels are pumped alternately, counter-phased, or 180+/−90 degrees outof phase, provides a superior ultrafiltration function and clearance ofsolutes from blood with respect to previously used roller pump andcentrifuged pump configurations. By use of experimental and numericalprocesses, the parameters influencing the transport phenomena across thedialyzer membrane, when counter-phased pulsatile flows are used in boththe blood and dialysate compartments of the dialyzer, exemplaryembodiments provided unexpected superior ultrafiltration and clearanceof toxic solutes from the blood over more expensive, heavy andpower-inefficient roller and centrifugal pumps configurations. Theresults of the exemplary dual channel pump configuration have beencompared with a configuration using standard roller pumps or centrifugepumps that are used in conventional dialysis equipment. Even though theflow of dialysate and blood generated by a roller pump flow resembles apulsatile flow, a lower amplitude flow and pressure is provided by aroller pump and its flow pulse is much longer than its non-flow or zeropressure pulse on the roller pump. Conversely, the pulsatile pumpprovides a substantially equally divided flow/high pressure pulse andno-flow/low pressure pulse.

The use of an exemplary dual channel pulsatile pump utilizes important,newly uncovered discoveries with respect to flow and pressure behaviorof certain fluids, such as blood and dialysate as they pass through adialyzer. Furthermore, improved clearance is established for ureacreatine and potassium thereby allowing the exemplary pump system tooperate at a slower rate for longer periods of time and use a mere 3 to5 watts of energy to operate the pumping. Furthermore, when using anexemplary pulsatile pump configuration with the filtration andabsorption section of an exemplary wearable or portable CRRT devicesubstantially twice the TMP (100-140 mmHg) was established across themembrane when compared with the TMP established with a roller pump orcentrifocal pump configuration. The reason for the improved TMP inexemplary embodiments is due to the counter-phased pulsatile flow of theblood and dialysate through the dialyzer establishing the difference inpressures between the blood within the fiber lumens and the dialysatechamber of the dialyzer.

Additional advantages of the exemplary dual channel pulsatileconfiguration for a wearable or portable CRRT device are that therelationship between the amount of ultrafiltration and the TMP is notlinear, as previously understood a roller and centrifuge pumpconfigurations. Instead the relationship between ultrafiltration and TMPbuilds to a nonlinear second order differential equation.

It is important to note that one of the important aspects of the dualchannel pulsatile pump configuration is its high efficiency in removingurea, creatine and other solutes from the blood. FIGS. 14A and 14B showhow the relevant concentration of solutes is transferred across themembrane over the axial length of a dialyzer with the blood anddialysate flowing opposite directions there through. In FIG. 14A theroller pump configuration is shown wherein the relative concentrationdrops off for the dialysate indicating that less solute is beingtransferred across the membrane at the blood output side of the dialyzerwith respect to the blood input side of the dialyzer. Conversely, inFIG. 14B, the relative concentration distribution or transfer of solutesfrom the blood to the dialysate is more linear and does not drop off. Itis believed the reason for this more evenly distributed distribution ofsolute transfer through the membrane and along the length of a lumenfiber in a dialyzer is due to the increased ultrafiltration across themembrane. The higher ultrafiltration rate caused by the higher TMPacross the membrane (due to the alternating pulsatile pumping of thedialysate and blood) results in enhanced convective forces which therebyresult in better mass transfer of solute across the membrane along theentire axial length of the fiber lumen inside the dialyzer. With theexemplary dual channel pulsatile pump configuration, convectionattributed to the 31% clearance of urea while in the roller pumpconfiguration the lack of the additional convection limited the ureatransfer to a mere 17%. Experimentation showed that the exemplarypulsatile pump configuration provided a 31% increase in convective masstransfer over the roller pump configuration. The exemplary high TMPcreated by the dual channel pulsatile pump configuration of an exemplaryembodiment provides enhanced clearance and ultrafiltration with a lowapproximate 2-5 watts of power required for the pump motor. This is anunexpected result when one compares it with the amount of energyrequired for a roller or centrifugal pump to pump dialysate or blood atsimilar flow rates through a dialyzer in a similar configuration. Thisis significant in that a small dual channel, battery operated andrechargeable wearable or portable dialysis device can be effectivelymanufactured and provide better performance than a large, heavy 120 voltAC powered set of roller or centrifugal pumps operating at similar flowrates.

A numerical simulation performed in addition to actual experimentationrevealed that the enhanced transmembrane transport of an exemplary dualchannel pulsatile pump configuration is primarily governed by diffusionacross the fiber membranes, but the transmembrane transport issignificantly increased over other pumping configurations due to theadded convection created by the large, pulsed TMP across the membrane,which was produced by the counter-phased pulsatile pumping of thedialysate and blood circuits. Furthermore, it is believed that theenhanced clearances achieved by exemplary embodiments may be attributedto a washout or push-pull-like effect associated with the pulsatileflows through and along the fiber membrane boundaries. Referring back toFIG. 6B, it is shown that the flows of the dialysate and blood in thedialyzer are each similarly equally spaced pulses having flow ratemaximums and minimums spaced substantially equally apart overpredetermined periods of time. A predetermined period of time for theexemplary embodiments were about 2 pulses per second, but it isunderstood that the various embodiments of the invention may have apulsatile pulsing flow rate of between about 0.5 and 4 pulses persecond, with flow rates ranging from about 20-100 ml/min during steadystate operation.

It will be appreciated by those skilled in the art having the benefit ofthis disclosure that this enhanced clearance in an artificial kidneyincorporating a pulsatile pump provides an energy efficient device forperforming dialysis. Such an exemplary device can be worn in-total on apatient as a completely wearable dialysis device or it may beincorporated into a portable device that may be carried or pushed (on acart) by the patient or medical personnel. It should be understood thatthe drawings and detailed description herein are to be regarded in anillustrative rather than a restrictive manner, and are not intended tobe limiting to the particular forms and examples disclosed. On thecontrary, included are any further modifications, changes,rearrangements, substitutions, alternatives, design choices, andembodiments apparent to those of ordinary skill in the art, withoutdeparting from the spirit and scope hereof, as defined by the followingclaims. Thus, it is intended that the following claims be interpreted toembrace all such further modifications, changes, rearrangements,substitutions, alternatives, design choices, and embodiments.

1. A continuous renal replacement therapy (CRRT) device comprising: adual channel ventricle pulsatile pump including: a blood pump channelfor providing a pulsed blood flow, said pulsed blood flow being periodicsuch that each period comprises a high blood pressure portion having afirst duration and a low blood pressure portion having a secondduration, said first duration and said second duration having a durationratio between about 3:4 and 4:3; and a dialysate pump channel forproviding a pulsed dialysate flow; said pulsed dialysate flow beingperiodic such that each period comprises a high dialysate pressureportion having said second duration and a low dialysate pressure portionhaving said first duration; wherein said high blood pressure portion andsaid low dialysate pressure portion occur, at least in part, during afirst periodic time frame; and a dialyzer comprising; a blood inlet forreceiving said pulsed blood flow; a plurality of fibers, each fibercomprising a semi permeable membrane exterior and a lumen extending thelength of the fiber, said lumen being for said pulsed blood flow to flowthrough; a blood outlet for said pulsed blood flow to exit saiddialyzer; a dialysate inlet for receiving said pulsed dialysate flow; adialysate chamber, about said plurality of fibers, for said pulseddialysate flow to flow through, said semi permeable membranes of saidplurality of fibers being between each said lumen and said dialysatechamber; and a dialysate outlet for said pulsed dialysate flow to exitsaid dialyzer; wherein said blood pump channel, said dialysate channeland said dialyzer are configured to establish a peak Trans MembranePressure (TMP) across said semi permeable membranes of wherein saidblood pump channel, said dialysate channel and said dialyzer areconfigured to establish a peak Trans Membrane Pressure (TMP) across saidsemi permeable membranes of said plurality of fibers and between saidpulsed blood flow in said lumens and said pulsed dialysate flow in saiddialysate chamber, said peak TMP occurring during said first periodictime frame, said peak TMP being between about 70 mmHg and 120 mmHg. 2.The CRRT device of claim 1, wherein said low blood pressure portion andsaid high dialysate pressure portion both occur, at least in part,during a second periodic time frame, and wherein said blood pumpchannel, said dialysate channel and said dialyzer are configured toestablish a minimum TMP across said semi permeable membranes of saidplurality of fibers and between said pulsed blood flow in said lumensand said pulsed dialysate flow in said dialysate chamber, and whereinsaid minimum TMP occurs during said second periodic time frame, saidminimum TMP being between about 10 mmHg and −10 mmHg.
 3. The CRRT deviceof claim 2, wherein the combination of said peak TMP that occurs duringsaid first periodic time frame and said minimum TMP that occurs duringsaid second periodic time frame inhibit clogging of said lumens and saidsemi permeable membranes.
 4. The CRRT device of claim 1, wherein saidblood pump channel and said dialysate pump channel are actuated by asame mechanical mechanism.
 5. The CRRT device of claim 1, wherein saidCRRT device is completely wearable on a patient.
 6. The CRRT device ofclaim 1, wherein said blood pump channel provides said pulsed blood flowwith a periodic flow rate of between 0.5 and 4 Hz and wherein saiddialysate pump channel provides a pulsed dialysate flow with saidperiodic flow rate.
 7. The CRRT device of claim 1, wherein said pulsedblood flow is a pulsatile blood flow.
 8. The CRRT device of claim 1,wherein said pulsed blood flow a pulsatile blood flow.